Neuroreasons for Clinical Depression by Charles Nemeroff

Charles Nemeroff, a writer for Scientific America, states both decreased activity of a neurotransmitter, as well as overactivity of a hormonal system, can lead to severe depression and, concurrently, suicide. Neurotransmitters travel between neurons, or nerve cells, in order to perform functions vital to life. Nemeroff states norepinephrine and serotonin, both monoamine type neurotransmitters, are natural anti-depressants. In order to understand the way these monoamines affect human biological make-up, it is necessary to have a brief understanding of the way neurotransmitters work.

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Between two neurons lies a small gap called the synapse. Neurotransmitters cross the synapse, being “fired” from one neuron and attaching to the next. Sometimes the receiving neuron will send out a message instructing the sending neuron to slow its rate of firing neurotransmitters. The sending neuron then has to pull the neurotransmitters back into itself, a process known as “reuptake”. Nemeroff points out that, due to overactive reuptake, reduced levels of norepinephrine have been noted in the brain of many depressed patients. Similarly, the study points out that in many patients who have committed suicide increased norepinephrine receptors were located in the brain’s cortex. Often receptors in the brain expand in number in order to compensate for low levels of transmitter molecules.

Due to these findings, reports Nemeroff, some drugs are now available that block norepinephrine reuptake and increase norepinephrine in the synapse, allowing it to act as an antidepressant. Serotonin is also a natural antidepressant and relates to drugs such as Prozac, which blocks serotonin reuptake. Nemeroff details how cells which produce serotonin often extend into many areas of the brain thought to contribute to depression, such as the hypothalamus. The drugs which prohibit serotonin reuptake are some of the most effective antidepressants ever made. Effexor is an especially effective drug because it blocks reuptake of serotonin and norepinephrine. Neurotransmitters are not the only biological elements which contribute to depression. Much research has been done that seems to show correlation between hormones and depression.

The hypothalamus regulates the hormonal system in the human body. As Nemeroff observed, the system that manages the body’s stress response is often singled out for causing severe depression. When there exists a physical or psychological threat to the body, the HPA-axis (hypothalamus-pituitary-adrenal) increases production of cortisol and, in effect, initiates the “fight or flight” function of the body. Nemeroff reports numerous studies show over-activation of the HPA-system may lead to depression. Because this system reacts to stress, however, it is unlikely that it will initiate itself without some type of anxiety-causing event. External sociological forces, coupled with increasingly negative psychological conflict, can cause the stress necessary to activate the HPA-system.

Biochemical functions, though extremely powerful and relevant to human behavior, rarely act alone. Simply because one may have a hyperactive HPA-axis or low levels of serotonin or norepinephrine monoamines, it is not definite a person will suffer from extreme depression or attempt suicide. Obviously emotions, though they may exist in chemical form, result from the ways people internalize and perceive external events as well as the ways in which people view themselves. The fact of the matter is people are strongly influenced by society, on conscious and subconscious levels. Society exists inside and outside of people, intermixing with the mind and with the psyche. The entire idea of consciousness is so complex and enigmatic, it is severely limiting to relate any aspect of it to only one particular school of science.

Nemeroff, 59, a psychiatrist at Emory University, is an internationally recognized expert on depression whose résumé spans 215 pages.


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He has treated some of Atlanta’s top business leaders, including Ted Turner, retired CNN head Tom Johnson and the late J.B. Fuqua, whose family has given $10 million to Emory to study and treat depression. Under Nemeroff’s leadership, Emory’s psychiatry department pulled in more than $22 million in National Institutes of Health grants just
last year.

From 2000 through 2006, Nemeroff received just over $960,000 from GlaxoSmithKline (GSK), but only disclosed no more than $35,000 to Emory. Between 2000 and 2007, he earned more than $2.8 million from various drug makers but failed to report at least $1.2 million. He signed a letter in 2004 promising Emory administrators that he would earn less than $10,000 a year from GSK but on the same day he was at a hotel earning $3,000 of what would become $170,000 in income from the company—17 times greater than the figure he agreed upon. He was the principal investigator for a five-year $3.9 billion grant financed by the NIMH for which GSK provided the drugs, during which he received more than the annual $10,000 threshold allowed from the company. In 2006, he stepped down as editor of Neuropsychopharmacology after publishing a favorable review of the vagus nerve stimulation (VNS) device, manufactured by Cyberonics, for which he was a paid consultant.  In 2003, he coauthored a favorable review of three therapies in Nature Neuroscience failing to mention his significant financial interests in these, including owning the patent for one of the treatments—a lithium patch.  Nemeroff has consulted for 21 drug and device companies simultaneously.  In 1991 Nemeroff testified before the FDA on behalf of Eli Lilly in hearings into Prozac, saying that the drug did not cause suicidal acts of ideation—yet 13 years later, the FDA concluded the opposite and issued a black box warning about suicide risks. Nemeroff resigned his position at Emory in 2008.

Now he’s a primary target of a U.S. Senate Finance Committee investigation into whether pharmaceutical money compromises the integrity of medical research and scholarship, an ethics controversy that has set the international world of academic medicine abuzz. Studies, speeches and articles can influence which drugs are prescribed for patients (2008).

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